Research of Biomarkers of Activity and Efficacy of BIBW2992 in Untreated Non-metastatic HNSCC Patients

NCT01415674 | Completed Phase 2

• 1 other identifier: GEP11/1010
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to identify predictive and pharmacodynamic biomarkers of activity and efficacy of pre-operative Afatinib (BIBW2992) in untreated non-metastatic head and neck squamous cell carcinoma patients

Conditions

Carcinoma, Squamous Cell of Head and Neck

Keywords

Squamous cell carcinoma of the head and neck; pre operative treatment; Afatinib; BIBW2992; Biological markers

Outcome Measures

Primary Outcomes (1)

• Potential predictive biological markers of activity of Afatinib

  Correlation between baseline potential biomarkers and 1. radiological response to Afatinib 2. FDG-PET response to Afatinib To identify the predictive biomarkers, the following translational researches will be carried out on initial tumor biopsy * IHC tumour characterization * High throughput protein analysis * Molecular analyses : FISH , Mutations by PCR , Quantitative RT-PCR

  15 days (FDG-PET evaluation) and about 21 days (CT scan or MRI evaluation) after start of treatment

Secondary Outcomes (4)

• Potential pharmacodynamic biological markers of activity of Afatinib

  15 days (FDG-PET evaluation) and about 21 days (CT scan or MRI evaluation) after start of treatment

• Efficacy of Afatinib

  about 21 days (CT scan or MRI evaluation) after start of treatment

• Toxicity of Afatinib

  every week until surgery.

• Pathological response

  on the surgical specimen

Study Arms (2)

Arm A: Afatinib 40mg per os daily

EXPERIMENTAL

Patients randomized to the arm A will take a single oral dose of Afatinib from Day 1, for 14 to 28 days, depending on the date of surgery. The number of dosing days will be chosen so that patients are off treatment for a maximum of 7 days before surgery.

Drug: Afatinib

Arm B : No pre operative treatment

NO INTERVENTION

Interventions

Afatinib DRUG

Afatinib 40mg per os daily for 14 to 28 days, depending on the date of the surgery

Also known as: BIBW2992

Arm A: Afatinib 40mg per os daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, amenable to curative treatment with surgery. Patients with a diagnosis of SCCHN of occult primary may be enrolled only with the agreement of the lead investigator upon review of the relevant clinical records
• T2-4N0-2 tumors (except T2N0 endolaryngeal tumors)
• Absence of metastases determined by PET CT scan
• Planned date of surgery allowing the patient to receive between 21 and 28 days of treatment
• ECOG performance status ≤ 2
• Adequate bone marrow function (absolute neutrophil count \> 1,000 cells/mm³, platelets \> 75,000 cells/mm³)
• Adequate liver function (total bilirubin ≤ 1.5 x UNL \[upper normal limit\], AST or ALT ≤ 3 x UNL)
• Adequate renal function (serum creatinine ≤ 1.5 x UNL)
• Adequate cardiac function (a normal left ventricular ejection fraction \[LVEF\] of ≥ 50% as measured by MUGA scan or echocardiogram within 4 weeks prior to start of study treatment)
• Potentially reproductive patients must agree to use an effective contraceptive method while on treatment
• Women of childbearing potential must have a negative serum beta-HCG pregnancy test within 7 days prior of enrollment and/or urine pregnancy 48 hours prior to the administration of the first study treatment
• Patients must be able to swallow tablets
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Patients must be affiliated to a Social Security System

You may not qualify if:

• Primary site of head and neck carcinoma in nasopharynx, or skin
• T1N0 tumors and T2N0 endolaryngeal tumors
• Patients not candidate for primary curative surgery
• Planning of surgery not allowing the patient to receive 21 to 28 days of treatment
• Patients receiving other anti-cancer medication such as chemotherapy, immunotherapy, biologic therapy or hormonal therapy (other than leuprolide or other GnRH agonists) within 30 days prior to the first dose of study drug and while on study treatment.
• Patients receiving other anti-cancer non-drug therapies: radiation, or tumor embolization within 4 weeks prior to the first dose of study drug and while on study treatment.
• Patient being treated with anti-vitamin K (AVK). Low molecular weight heparin (LMWH) is allowed.
• Patient with uncontrolled infection
• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes,
• Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification \> III, unstable angina, myocardial infarction within six months prior to randomisation, or poorly controlled arrhythmia, chronic liver or renal disease, severely impaired lung function
• Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE grade \>1 diarrhea of any etiology at randomisation
• Known pre-existing Interstitial Lung Disease (ILD)
• Patients requiring comedication with potent P-gp inhibitors (including Cyclosporin, Erythromycin, Ketoconazole, Itraconazole, Quinidine, Phenobarbital salt with Quinidine, Ritonavir, Valspodar, Verapamil) or inducers (including St John's wort, rifampicin)
• Patients with a known HIV, active hepatitis B and/or C infection
• Pregnant women, women who are likely to be pregnant or are breast-feeding

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (11)

CHU d'Angers

Angers, France

Location

Institut de cancérologie de l'Ouest - Site Paul Papin

Angers, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Chu de Nantes

Nantes, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75248, France

Location

Institut de cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Christophe Le Tourneau

  Institut Curie Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2011
• First Posted: August 12, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: February 2, 2022

Record last verified: 2022-02

Locations

FR (11)